Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus

Ann Med. 2023;55(2):2238600. doi: 10.1080/07853890.2023.2238600.

Abstract

Introduction: Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action.

Methods: A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured.

Results: After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend.

Conclusion: Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

Keywords: Low-dose interleukin-2; autoimmune thyroid disease; therapy.

Plain language summary

Low-dose IL-2 could decrease the levels of TG-Ab and TPO-Ab in AITD with concurrent SLE patients.Low-dose IL-2 may regulate Treg/Tfh balance and B-cells to ameliorate TG-Ab and TPO-Ab.Low-dose IL-2 provides a new avenue for AITD clinical treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Interleukin-2
  • Lupus Erythematosus, Systemic*
  • Retrospective Studies
  • Thyroid Diseases*
  • Thyroxine
  • Triiodothyronine

Substances

  • Interleukin-2
  • Thyroxine
  • Triiodothyronine

Grants and funding

This work was supported by the National Key R&D Program of China (No. 2022YFE0131700), Beijing sci-Tech Program (Z191100006619114), National Natural Science Foundation of China (81701607, 82071813 and 8227183), and Peking University People’s Hospital Scientific Research Development Funds (RDZH2022-03).